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Dev Biol. 2017 Nov 15;431(2):168-178. doi: 10.1016/j.ydbio.2017.09.026. Epub 2017 Sep 21.

Neural crest cells utilize primary cilia to regulate ventral forebrain morphogenesis via Hedgehog-dependent regulation of oriented cell division.

Author information

1
Division of Plastic Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
2
Division of Plastic Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: samantha.brugmann@cchmc.org.

Abstract

Development of the brain directly influences the development of the face via both physical growth and Sonic hedgehog (SHH) activity; however, little is known about how neural crest cells (NCCs), the mesenchymal population that comprise the developing facial prominences, influence the development of the brain. We utilized the conditional ciliary mutant Wnt1-Cre;Kif3afl/fl to demonstrate that loss of primary cilia on NCCs resulted in a widened ventral forebrain. We found that neuroectodermal Shh expression, dorsal/ventral patterning, and amount of proliferation in the ventral neuroectoderm was not changed in Wnt1-Cre;Kif3afl/fl mutants; however, tissue polarity and directional cell division were disrupted. Furthermore, NCCs of Wnt1-Cre;Kif3afl/fl mutants failed to respond to a SHH signal emanating from the ventral forebrain. We were able to recapitulate the ventral forebrain phenotype by removing Smoothened from NCCs (Wnt1-Cre;Smofl/fl) indicating that changes in the ventral forebrain were mediated through a Hedgehog-dependent mechanism. Together, these data suggest a novel, cilia-dependent mechanism for NCCs during forebrain development.

KEYWORDS:

Hedgehog signaling; Sox10-Cre; Wnt1-Cre; neural crest; primary cilia; ventral forebrain

PMID:
28941984
PMCID:
PMC5658255
DOI:
10.1016/j.ydbio.2017.09.026
[Indexed for MEDLINE]
Free PMC Article

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