Ttc21b is required for proper forebrain neural progenitor proliferation Article Swipe
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· 2025
· Open Access
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· DOI: https://doi.org/10.1242/dmm.052392
· OA: W4417271397
Primary cilia play a pivotal role in cellular signaling and development. Human primary microcephaly is strongly associated with pathogenic variants in primary cilia genes. Here, we examine the role of Ttc21b, a component of the intraflagellar transport-A complex, in mouse forebrain development using a Ttc21balien null allele. Our findings reveal significant microcephaly in homozygous mutants is caused by disrupted neural progenitor proliferation and differentiation. Histological and immunohistochemical analyses show an enlarged ventricular zone and reduced cortical plate thickness, accompanied by altered mitotic spindle angles, suggesting defects in symmetric versus asymmetric cell divisions. Embryonic expression patterns suggest that perdurant TTC21B protein may underlie these phenotypes. Progenitor proliferation kinetics were disrupted along with changes in TBR2-positive intermediate progenitors and TBR1-positive early born neurons. Neuronal processes in the cortical plate were significantly shortened. Our findings support a model in which early Ttc21b expression in precursors destined for the forebrain is critical to make TTC21B protein for sustaining later neural progenitor proliferation and differentiation. These results advance our understanding of primary cilia in cortical development.
