Absence of Twisted Gastrulation (Twsg1) Limits the Population of Cranial Neural Crest Cells

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Absence of Twisted Gastrulation (Twsg1) Limits the Population of Cranial Neural Crest Cells

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2009-04-08

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Craniofacial defects are among the most common birth defects with cranial neural crest cells (NCCs) playing a fundamental role in craniofacial development. The cranial NCCs migrate from dorsal neural folds to populate the branchial arches. Then they differentiate into the cells that form facial structures. For example, the mandible forms from the first branchial arch (BA1). Twisted gastrulation (Twsg1) is a gene that has been found to influence craniofacial development. A mutation in Twsg1 in mice produces a spectrum of craniofacial defects ranging from normal appearance to underdevelopment of the mandible, midline facial defects, and forebrain defects resulting in holoprosencephaly. Previous research has shown that Twsg1 acts as a bone morphogenetic protein (BMP) antagonist and thereby limits apoptosis in BA1, a key destination of cranial NCCs. Apoptosis is increased in BA1 in the absence of Twsg1, leading to a loss of BA1 derivatives. The hypothesis of this work is that the absence of Twsg1 also increases apoptosis in the cranial NCCs and thereby limits the population of NCCs prior to their migration to BA1. This study focused on determining whether the NCC population was depleted in Twsg1 knockout mice and whether the midbrain region itself was affected. We found that the midbrain markers were normal, but the markers specific for NCCs were significantly reduced. This reduction is consistent with a depletion of the NCC population. Future research will directly study proliferation, apoptosis, and BMP signaling in NCC populations in the absence of Twsg1.

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Additional contributors: Ashley Peterson; Cynthia Forsman-Earl; Anna Petryk (faculty mentor).

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Mittelstaedt, Gina. (2009). Absence of Twisted Gastrulation (Twsg1) Limits the Population of Cranial Neural Crest Cells. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/50352.

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