Fate Of Cranial Neural Crest Cells Research Articles

Regulation of cranial neural crest cell fate by Irf6 and Twist1 interaction

A wide variety of common craniofacial birth defects and pediatric cancers arise from errors in the development of cranial neural crest cells (CNCC) that give rise to craniofacial skeletal and peripheral nervous systems. Identification of the genetic and environmental factors that regulate cell fate of CNCCs is crucial for uncovering the causes behind craniofacial disorders. Our lab has identified a dual‐transcription factor pathway that regulates CNCCs during EMT and migration. Initially, we identified a causative mutation in a TWIST1 binding site within an Interferon Regulatory Factor 6 (IRF6) enhancer in a multi‐generational family affected with syndromic cleft lip and palate called Van der Woude syndrome. Our subsequent animal work has shown that Twist1 and Irf6 genetically interact during early craniofacial development, and that the compound heterozygotes exhibit craniofacial abnormalities. We recently demonstrated that Irf6 is required for neural tube and CNCC development and that it interacts with Twist1 during EMT and migration of CNCCs. We also showed that TWIST1 is highly phosphorylated in CNCCs and its phosphorylation is crucial for regulating Irf6 and potentially miR10 family members in CNCC‐derived craniofacial tissues. Our recent in‐vivo and neural tube explants using dual fluorescent cell tracing system showed that Twist1 conditional knockout (CKO) in CNCCs significantly reduced cell delamination and disrupted EMT. The detached Twist1 CKO in CNCCs retained their epithelial signatures and migrated as clusters of epithelial‐like cells over significantly shorter distances. Finally, Twist1 phospho‐incompetent mice for two serine residues were recently generated to determine their impact on TWIST1 activity. Our preliminary results showed that Twist1S68A/S68A phospho‐mutant mice have craniofacial bone defects and forebrain hemorrhage.Support or Funding InformationUTHealth start‐up funds and a small grant from theRolanette and Berdon Lawrence Bone Disease Program of Texas

Retinoic acid receptor isoform β2 is an early marker for alimentary tract and central nervous system positional specification in the chicken

In this study I describe the distribution of one variant of retinoic acid receptor-beta (RAR-beta), the RAR-beta 2 isoform, during the stages before organogenesis of the chick embryo. Unlike the situation in older embryos, at these stages its distribution does not differ qualitatively from that of all RAR-beta transcripts. During the presomite headfold stage, RAR-beta 2 transcripts are simultaneously upregulated in two different locations. These locations define positional identities within the anlage of the chick alimentary tract and within the central nervous system (CNS). As development proceeds the transcript expression maintains its spatial restriction within those two regions. At presomite stages RAR-beta 2 transcripts are enriched within the proamnion, which contains the presumptive foregut and precardiac cells; somewhat later it is present within the foregut endoderm at the site where foregut and the lateral amniocardiac vesicles fuse to form the coelom and cardiac tube. As the foregut continues its caudal extension, RAR-beta 2 expression defines an anteroposterior boundary at the level of the pharynx within the alimentary tract. The second expression site of RAR-beta 2 mRNA first appears within the posterior neural plate at the level where Hensen's node commences its caudal regression. This boundary lies at the border between the future rhombomeres 5 and 6 within the hindbrain. Expression of RAR-beta 2 transcripts is also spatially restricted within some migrating cranial neural crest cells. The expression of RAR-beta 2 in cranial neural crest cells is consistent with what is known about the mechanisms by which cranial neural crest cell fate is determined. These data support the hypothesis that retinoids may contribute to positional specification of anteroposterior body axis, and perhaps also to the formation and identity of the developing alimentary tract and heart tube.