The lung is composed of endoderm derived epithelial cells that constitute the luminal surface of the airways and alveolar spaces. Ensheathing the epithelium are mesenchymal derivatives including airway smooth muscle, pulmonary fibroblasts, and vascular endothelium. During development, the epithelium and mesenchyme are involved in a complex circuit of paracrine and autocrine signals that act to drive morphogenesis and patterning of the developing airway structure. The lung initially arises from the anterior foregut endoderm region, which itself arises from the definitive endoderm that develops soon after gastrulation. .
Citation:Lessons from development for directing lung endoderm differentiation in pluripotent stem cells Rachel S. Kadzik and Edward E. Morrisey Cell Stem Cell. Author manuscript; available in PMC 2013 Apr 6. Published in final edited form as: Cell Stem Cell. 2012 Apr 6; 10(4): 355–361. doi: 10.1016/j.stem.2012.03.013 PMCID: PMC3366272 NIHMSID: NIHMS367732 PMID: 22482501
In response to a signal from the ureter 尿管, mesenchymal cells condense, aggregate into pretubular clusters and undergo an epithelial conversion generating a simple tubule. This then undergoes morphogenesis and is transformed into the excretory system of the kidney, the nephron. We report here that the expression of Wnt-4, which encodes a secreted glycoprotein, correlates with, and is required for, kidney tubulogenesis. Mice lacking Wnt-4 activity fail to form pretubular cell aggregates; however, other aspects of mesenchymal and ureteric development are unaffected. Thus, Wnt-4 appears to act as an autoinducer of the mesenchyme to epithelial transition that underlies nephron development. (Nature . 1994 Dec 15;372(6507):679-83. doi: 10.1038/372679a0. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4 K Stark 1, S Vainio, G Vassileva, A P McMahon https://pubmed.ncbi.nlm.nih.gov/7990960/)
Development of the Human Penis and Clitoris Differentiation. 2018 Sep-Oct; 103: 74–85. Published online 2018 Aug 23. doi: 10.1016/j.diff.2018.08.001 PMCID: PMC6234061
The cell biology and molecular genetics of Müllerian duct development January 2018 Wiley Interdisciplinary Reviews: Developmental Biology 7(2):e310 DOI:10.1002/wdev.310 ResearchGate
Herrera AM, Cohn MJ. Embryonic origin and compartmental organization of the external genitalia. Sci Rep. 2014 Nov 5;4:6896. doi: 10.1038/srep06896. PMID: 25372631; PMCID: PMC4894444. the genital tubercle, the precursor of the penis and clitoris, arises from two populations of progenitor cells that originate at the lateral edges of the embryo, at the level of the posterior hindlimb buds and anterior tail. During body wall closure, the left and right external genital progenitor pools are brought together at the ventral midline, where they form the paired genital swellings that give rise to the genital tubercle.
Lin C, Yin Y, Veith GM, Fisher AV, Long F, Ma L. Temporal and spatial dissection of Shh signaling in genital tubercle development. Development. 2009 Dec;136(23) 3959-3967. doi:10.1242/dev.039768. PMID: 19906863; PMCID: PMC2778743.
HOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endothelia Carley A. Shaut, Chie Saneyoshi, Emily A. Morgan, Wendy M. Knosp, Diane R. Sexton, H. Scott Stadler 15 February 2007 https://doi.org/10.1002/dvdy.21077
Unique functions of Sonic hedgehog signaling during external genitalia
Length of fingers and penis are related through fetal Hox gene expression Martin Voracek, D.Sc. John T. Manning, Ph.D. LETTER TO THE EDITOR Urology VOLUME 62, ISSUE 1, P201, JULY 2003 DOI:https://doi.org/10.1016/S0090-4295(02)02598-0
Mortlock, D., Innis, J. Mutation of HOXA13 in hand-foot-genital syndrome . Nat Genet15, 179–180 (1997). https://doi.org/10.1038/ng0297-179 We report the identification of a HOXA13 nonsense mutation in a family with hand-foot-genital syndrome.
Hand-foot-genital syndrome Variants (also called mutations) in the HOXA13 gene cause hand-foot-genital syndrome. The HOXA13 gene provides instructions for producing a protein that plays an important role in development before birth. Specifically, this protein appears to be critical for the formation and development of the limbs (particularly the hands and feet), urinary tract, and reproductive system.
Epithelial-Mesenchymal Interactions in Development of the Mouse Fetal Genital Tubercle Eric A. Kurzrock; Laurence S. Baskin; Yingwu Li; Gerald R. Cunha Cells Tissues Organs (1999) 164 (3): 125–130 The mesenchyme of the adult mouse penis consists of a corpus cavernosum and proximal and distal bones. The differentiation of penile mesenchyme into bone and cartilage begins after birth and can be accelerated by androgens.
Induction of Pluripotency by Defined Factors (1:09:50) NIH VideoCast チャンネル登録者数 3.92万人 NIH Director’s Wednesday Afternoon Lectures Air date: Thursday, January 14, 2010, 3:00:00 PM
Review articles
Review Article GLIS1-3: emerging roles in reprogramming, stem and progenitor cell differentiation and maintenance David W. Scoville, Hong Soon Kang, Anton M. Jetten Published: 27 September 2017. doi: 10.21037/sci.2017.09.01 The GLI Similar 1-3 (GLIS) proteins form a subfamily of Krüppel-like zinc finger transcription factors that are closely-related to the GLI and ZIC subfamilies (1–8). Members of these three subfamilies share a highly homologous DNA binding domain (DBD) consisting of five Cys2His2-type zinc finger motifs. However, these proteins exhibit little homology outside their DBD region. … Initial overexpression of OCT3/4 (POU5F1), SOX2, and KLF4 (OSK) are widely used for the reprogramming of somatic cells into iPSCs (32). However, the efficiency of generating iPSCs is very low, which has been attributed to difficulties in overcoming epigenetics barriers in the starting cell (33). Co-expression of C-MYC increases the efficiency, but also enhances the potential tumorigenicity of iPSC-derived differentiated cells. Recently, using a screen analyzing 1,437 transcription factors for their ability to promote reprogramming efficiency, GLIS1 was found to greatly enhance the number of iPSC colonies generated when co-expressed with OSK (referred to as OSKG) in either human or mouse dermal fibroblasts (29,34). Inversely, down-regulation of GLIS1 expression by shRNAs reduced the OSK-induced generation of iPSC colonies in mouse fibroblasts suggesting that endogenous GLIS1 is able to promote OSK-mediated reprogramming.
Ye L, Swingen C, Zhang J. Induced pluripotent stem cells and their potential for basic and clinical sciences. Curr Cardiol Rev. 2013 Feb 1;9(1):63-72. doi: 10.2174/157340313805076278. PMID: 22935022; PMCID: PMC3584308. Later, it was shown that iPS cells can be generated from fibroblasts by viral integration of Oct4/Sox2/Klf4without c-Myc [4]. Although these iPS cells showed reduced tumorigenicity in chimeras and progeny mice, the reprogramming process is much slower, and efficiency is substantially reduced.
Schmidt R, Plath K. The roles of the reprogramming factors Oct4, Sox2 and Klf4 in resetting the somatic cell epigenome during induced pluripotent stem cell generation. Genome Biol. 2012 Oct 22;13(10):251. doi: 10.1186/gb-2012-13-10-251. PMCID: PMC3491406. The most well known of these enhancer factors is c-Myc, which was added alongside O, S and K in the original reprogramming experiment but later shown to be dispensible [1,5,9,10,15,16].
Takahashi K, Mitsui K, Yamanaka S. Role of ERas in promoting tumour-like properties in mouse embryonic stem cells. Nature. 2003 May 29;423(6939):541-5. doi: 10.1038/nature01646. PMID: 12774123. (Yamanaka moved to Kyoto University in 2005. Yamanaka asked Kazu Takahashi to take over the project (24 candidate genes for reprogramming). Yamanaka knew that the project was risky but thought it was ok for the next a couple of years without papers as Takahashi published this Nature paper.(https://www.youtube.com/watch?v=AD1sZU1yk-Y 33:07))
Original articles
Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1 Momoko Maekawa, Kei Yamaguchi, Tomonori Nakamura, Ran Shibukawa, Ikumi Kodanaka, Tomoko Ichisaka, Yoshifumi Kawamura, Hiromi Mochizuki, Naoki Goshima, and Shinya Yamanaka Nature, Volume: 474, Pages: 225-229, Date published: 09 June 2011, DOI: 10.1038/nature10106
Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2008;26:101–106. doi: 10.1038/nbt1374.
Wernig M, Meissner A, Cassady JP, Jaenisch R. c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell. 2008;2:10–12. doi: 10.1016/j.stem.2007.12.001.
Other papers
Tapia, N., MacCarthy, C., Esch, D. et al. Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency. Sci Rep5, 13533 (2015). https://doi.org/10.1038/srep13533
3D Heart Tube Embryology – Myoepicardial mantle – Proepicardial organ – CVS Embryology MedicoVisual – Visual Medical Lectures チャンネル登録者数 4.81万人 https://www.youtube.com/watch?v=tcM7DOSoabI
https://staff.um.edu.mt/acus1/Heart-a.htm
心臓の初期発生
Molecular Regulation of Cardiomyocyte Differentiation Sharon L. Paige, Karolina Plonowska, Adele Xu and Sean M. Wu Originally published16 Jan 2015https://doi.org/10.1161/CIRCRESAHA.116.302752Circulation Research. 2015;116:341–353
心筋分化とWNTシグナルのタイミング
World J Stem Cells. Aug 26, 2023; 15(8): 821-841 Published online Aug 26, 2023. doi: 10.4252/wjsc.v15.i8.821 Wnt signaling pathway inhibitor promotes mesenchymal stem cells differentiation into cardiac progenitor cells in vitro and improves cardiomyopathy in vivo Muneer R, Qazi REM, Fatima A, Ahmad W, Salim A, Dini L, Khan I. Wnt signaling pathway inhibitor promotes mesenchymal stem cells differentiation into cardiac progenitor cells in vitro and improves cardiomyopathy in vivo. World J Stem Cells 2023; 15(8): 821-841 [PMID: 37700819 DOI: 10.4252/wjsc.v15.i8.821] https://www.wjgnet.com/1948-0210/full/v15/i8/821.htm
Fu, Wb., Wang, W.E. & Zeng, Cy. Wnt signaling pathways in myocardial infarction and the therapeutic effects of Wnt pathway inhibitors.Acta Pharmacol Sin40, 9–12 (2019). https://doi.org/10.1038/s41401-018-0060-4
Wnt/β-Catenin Signaling during Cardiac Development and Repair J. Cardiovasc. Dev. Dis. 2014, 1(1), 98-110; https://doi.org/10.3390/jcdd1010098 https://www.mdpi.com/2308-3425/1/1/98
The Multiple Phases and Faces of Wnt Signaling During Cardiac Differentiation and Development Susanne Gessert and Michael Kühl Originally published23 Jul 2010https://doi.org/10.1161/CIRCRESAHA.110.221531 Circulation Research. 2010;107:186–199
Eldad Tzahor, Wnt/β-Catenin Signaling and Cardiogenesis: Timing Does Matter, Developmental Cell, Volume 13, Issue 1, 2007, Pages 10-13, ISSN 1534-5807, https://doi.org/10.1016/j.devcel.2007.06.006. the Wnt/β-catenin pathway plays distinct, even opposing, roles during various stages of cardiac development. WNTシグナルは、心筋分化において、働くタイミングに応じてポジティブにもネガティブにも働く
Biphasic role for Wnt/β-catenin signaling in cardiac specification in zebrafish and embryonic stem cells Shuichi Ueno, Gilbert Weidinger, Tomoaki Osugi, +5, and Charles E. Murry murry@u.washington.eduAuthors Info & Affiliations June 5, 2007 104 (23) 9685-9690 https://doi.org/10.1073/pnas.0702859104 Developmental studies indicate that the Wnt/β-catenin pathway negatively regulates cardiac differentiation, whereas studies with pluripotent embryonal carcinoma cells suggest that this pathway promotes cardiogenesis. This apparent contradiction led us to hypothesize that Wnt/β-catenin signaling acts biphasically, either promoting or inhibiting cardiogenesis depending on timing. WNTシグナルは、心筋分化において、働くタイミングに応じてポジティブにもネガティブにも働く
Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors Chulan Kwon, Joshua Arnold, Edward C. Hsiao, +2, and Deepak Srivastava dsrivastava@gladstone.ucsf.eduAuthors Info & Affiliations Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved May 21, 2007 June 26, 2007 104 (26) 10894-10899 https://doi.org/10.1073/pnas.0704044104
Aortic Arches – Embryology in 3 minutes Medical Snippet チャンネル登録者数 3.44万人
Aortic Arches and Large Arteries: Introduction by Peter Ward, PhD https://app.lecturio.com/#/lecture/c/7332/44490
Development of aortic arch arteries & development of vertebral artery easy humananatomy チャンネル登録者数 1.55万人 https://www.youtube.com/watch?v=pwRjEBabH8Y ventral aortaとdorsal aortaの説明から入っています。
Bjarke Jensen, Tobias Wang, Vincent M. Christoffels, Antoon F.M. Moorman, Evolution and development of the building plan of the vertebrate heart, Biochimica et Biophysica Acta (BBA) – Molecular Cell Research, Volume 1833, Issue 4, 2013, Pages 783-794, ISSN 0167-4889, https://doi.org/10.1016/j.bbamcr.2012.10.004. The heart of the earliest vertebrates, possibly represented by Amphioxus, was probably a contractile vessel where peristaltic movements provide the perfusion of the vasculature at low pressures.
Optimal morphometric factors responsible for enhanced gas exchange in fish gillshttps://arxiv.org/abs/1805.07744 魚のエラの構造がわかりやすい図が掲載されている
Fate of the Primitive Streak, Teratomas, formation of the Notochord, Diastematomyelia, Chordoma, + Douglas Gillard, DC, Professor of Clinical Science チャンネル登録者数 6.49万人
Somite (Wikipedia) The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryonic stage of somitogenesis, along the head-to-tail axis in segmented animals. In vertebrates, somites subdivide into the dermatomes, myotomes,sclerotomes and syndetomes that give rise to the vertebrae of the vertebral column, rib cage, part of the occipital bone, skeletal muscle, cartilage, tendons, and skin (of the back).
Dermatomes and Cutaneous fields The Noted Anatomist チャンネル登録者数 55.6万人 (10:57) 筋肉を支配する運動神経と皮膚からの感覚を脊髄に伝える感覚神経とは場所的に関連するので、併せてここで学ぶほうが頭が整理されます。（発生学的な由来はとりあえずおいておいて）
Myotome https://www.physio-pedia.com/Myotomes A myotome (greek: myo=muscle, tome = a section, volume) is defined as a group of muscles which is innervated by single spinal nerve root.
Dermatomes
Dermatomes The Noted Anatomist チャンネル登録者数 55.6万人 (11:47)
During vertebrate development, the central (CNS) and peripheral nervous systems (PNS) arise from the neural plate. Cells at the margin of the neural plate give rise to neural crest cells, which migrate extensively throughout the embryo, contributing to the majority of neurons and all of the glia of the PNS. The rest of the neural plate invaginates to form the neural tube, which expands to form the brain and spinal cord.
From classical to current: analyzing peripheral nervous system and spinal cord lineage and fate Dev Biol. 2015 Feb 15; 398(2): 135–146. PMCID: PMC4845735
Arnold Kriegstein (UCSF) 1: Outer Subventricular Zone Radial Glia Cells – Brain Development Science Communication Lab チャンネル登録者数 17.7万人
10:20- single-labelled subcortical cells time lapse imaging
11:43 “we were very lucky at UCSF to get donated tissue”
*Gestational age is measured in weeks, from the first day of the woman’s last menstrual cycle to the current date. https://medlineplus.gov/ency/article/002367.htm
David V. Hansen, Jan H. Lui, Philip R. L. Parker & Arnold R. Kriegstein. Neurogenic radial glia in the outer subventricular zone of human neocortex.Nature464, 554–561 (2010). https://doi.org/10.1038/nature08845
Stephen C. Noctor, Alexander C. Flint, Tamily A. Weissman, Ryan S. Dammerman & Arnold R. Kriegstein. Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714–720 (2001). https://doi.org/10.1038/35055553 (全文は有料） It has been suggested that radial glia may be neuronal precursors, but this has not been demonstrated in vivo. We have used a retroviral vector encoding enhanced green fluorescent protein to label precursor cells in vivo and have examined clones 1–3 days later using morphological, immunohistochemical and electrophysiological techniques. Here we show that clones consist of mitotic radial glia and postmitotic neurons, and that neurons migrate along clonally related radial glia. Time-lapse images show that proliferative radial glia generate neurons.
成人の脳ではあらたに神経細胞（ニューロン）がつくられることはないと長い間信じられてきて医学部の学部教育でもそう教えられてきましたが、その常識は最近覆りました。脳の一部の領域ではニューロンが成人の脳でも作られていることが発見されたのです。ニューロンが新生する(neurogenesis)領域の一つが海馬で、もうひとつがsubventricular zone (SVZ)と呼ばれる領域です。
Adult neurogenesis, the process of creating new neurons, involves the coordinated division, migration, and differentiation of neural stem cells. This process is restricted to neurogenic niches located in two distinct areas of the brain: the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle, where new neurons are generated and then migrate to the olfactory bulb.
1960s New neurons could be generated in the DG and SVZ of the adult brain in cat and rat models (Altman, 1962, 1963; Altman and Das, 1965)
1989 Adult brain neurogenesis in songbirds (Nottebohm, 1989).
1998 Neurogenesis in the adult human hippocampus (in the postmortem tissue of cancer patients) (Eriksson et al., Nat Med. 1998 Nov;4(11):1313-7. ).
1999 Adult macaque monkeys neurogenesis ten times lower than that of rodents (Gould et al., 1999)
2013 carbon dating techniques to determine that the human DG adds up to 700 neurons per day (Spalding et al., 2013)
Kheirbek MA, Hen R. (Radio)active neurogenesis in the human hippocampus. Cell. 2013 Jun 6;153(6):1183-4. doi: 10.1016/j.cell.2013.05.033. PMID: 23746833; PMCID: PMC4046854. (Author manuscript)
2018 studies using carbon 14 can produce unreliable results and are prone to noise and contamination (Sorrells et al., 2018).
Hussain et al. Adult neurogenesis: a real hope or a delusion? Neural Regen Res. 2024 Jan;19(1):6-15. doi: 10.4103/1673-5374.375317. PMCID: PMC10479850.
The Adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis Daniel A. Lim and Arturo Alvarez-Buylla Cold Spring Harb Perspect Biol. 2016 May; 8(5): a018820. doi: 10.1101/cshperspect.a018820 PMCID: PMC4852803
