Talk:Embryology History - Nicole Le Douarin

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Cite this page: Hill, M.A. (2024, May 26) Embryology Embryology History - Nicole Le Douarin. Retrieved from



The neural crest, a multifaceted structure of the vertebrates

Birth Defects Res C Embryo Today. 2014 Sep;102(3):187-209. doi: 10.1002/bdrc.21080. Epub 2014 Sep 15.

Dupin E1, Le Douarin NM.


In this review, several features of the cells originating from the lateral borders of the primitive neural anlagen, the neural crest (NC) are considered. Among them, their multipotentiality, which together with their migratory properties, leads them to colonize the developing body and to participate in the development of many tissues and organs. The in vitro analysis of the developmental capacities of single NC cells (NCC) showed that they present several analogies with the hematopoietic cells whose differentiation involves the activity of stem cells endowed with different arrays of developmental potentialities. The permanence of such NC stem cells in the adult organism raises the problem of their role at that stage of life. The NC has appeared during evolution in the vertebrate phylum and is absent in their Protocordates ancestors. The major role of the NCC in the development of the vertebrate head points to a critical role for this structure in the remarkable diversification and radiation of this group of animals. © 2014 Wiley Periodicals, Inc. KEYWORDS: evolution; lineage; neural crest

PMID 25219958;jsessionid=4AA5004C9E79F16634412AB3D2FD4125.f01t01

Sonic Hedgehog promotes the survival of neural crest cells by limiting apoptosis induced by the dependence receptor CDON during branchial arch development

Biochem Biophys Res Commun. 2014 Sep 26;452(3):655-60. doi: 10.1016/j.bbrc.2014.08.134. Epub 2014 Sep 1.

Delloye-Bourgeois C1, Rama N1, Brito J2, Le Douarin N2, Mehlen P3.


Cell-adhesion molecule-related/Downregulated by Oncogenes (CDO or CDON) was identified as a receptor for the classic morphogen Sonic Hedgehog (SHH). It has been shown that, in cell culture, CDO also behaves as a SHH dependence receptor: CDO actively triggers apoptosis in absence of SHH via a proteolytic cleavage in CDO intracellular domain. We present evidence that CDO is also pro-apoptotic in the developing neural tube where SHH is known to act as a survival factor. SHH, produced by the ventral foregut endoderm, was shown to promote survival of facial neural crest cells (NCCs) that colonize the first branchial arch (BA1). We show here that the survival activity of SHH on neural crest cells is due to SHH-mediated inhibition of CDO pro-apoptotic activity. Silencing of CDO rescued NCCs from apoptosis observed upon SHH inhibition in the ventral foregut endoderm. Thus, the pair SHH/dependence receptor CDO may play an important role in neural crest cell survival during the formation of the first branchial arch. Copyright © 2014 Elsevier Inc. All rights reserved. KEYWORDS: Apoptosis; CDO; Dependence receptors; Embryonic development; Neural crest cells

PMID 25193697

Combinatorial activity of Six1-2-4 genes in cephalic neural crest cells controls craniofacial and brain development

Cell Mol Life Sci. 2014 Jun;71(11):2149-64. doi: 10.1007/s00018-013-1477-z. Epub 2013 Sep 24.

Garcez RC1, Le Douarin NM, Creuzet SE.


The combinatorial expression of Hox genes is an evolutionarily ancient program underlying body axis patterning in all Bilateria. In the head, the neural crest (NC)--a vertebrate innovation that contributes to evolutionarily novel skeletal and neural features--develops as a structure free of Hox-gene expression. The activation of Hoxa2 in the Hox-free facial NC (FNC) leads to severe craniofacial and brain defects. Here, we show that this condition unveils the requirement of three Six genes, Six1, Six2, and Six4, for brain development and morphogenesis of the maxillo-mandibular and nasofrontal skeleton. Inactivation of each of these Six genes in FNC generates diverse brain defects, ranging from plexus agenesis to mild or severe holoprosencephaly, and entails facial hypoplasia or truncation of the craniofacial skeleton. The triple silencing of these genes reveals their complementary role in face and brain morphogenesis. Furthermore, we show that the perturbation of the intrinsic genetic FNC program, by either Hoxa2 expression or Six gene inactivation, affects Bmp signaling through the downregulation of Bmp antagonists in the FNC cells. When upregulated in the FNC, Bmp antagonists suppress the adverse skeletal and cerebral effects of Hoxa2 expression. These results demonstrate that the combinatorial expression of Six1, Six2, and Six4 is required for the molecular programs governing craniofacial and cerebral development. These genes are crucial for the signaling system of FNC origin, which regulates normal growth and patterning of the cephalic neuroepithelium. Our results strongly suggest that several congenital craniofacial and cerebral malformations could be attributed to Six genes' misregulation.

PMID 24061537


Developmental hematopoiesis: historical background and perspectives. An interview with Nicole le Douarin. Interview by Charles Durand and Thierry Jaffredo.

Int J Dev Biol. 2010;54(6-7):951-4. doi: 10.1387/ijdb.103154cd.


Nicole le Douarin has shown a long lasting interest for developmental hematopoiesis. Starting from her early research experience, we travel along the main discoveries and concepts that have shaped the modern view of developmental hematopoiesis. All through, we survey the seminal contribution of the "Ecole de Nogent" about lymphocyte homing and the discovery of endothelial-specific tyrosine kinases. This interview is a promenade through the past and present of developmental hematopoiesis narrated by an exceptional personality and an outstanding scientist.

PMID 20711976