The Grizzly, March 26, 1990

Wismer Plans Alternatives • Reaction to Idaho Law • 101 Blaze Update • Letters: Cleaning Service Working?; Fix, Please! • Broaden our Horizons • Sex and Religion • Doughty Discusses Seminar • Time is Now for Men\u27s Lacrosse • Bears Win First • Track Team Beats the Cold • Hackers No More • Tennis Sweep • Bears Roll • Comedy Plays at Ritter • This Week\u27s Video Reviews • Fun With Jell-Ohttps://digitalcommons.ursinus.edu/grizzlynews/1255/thumbnail.jp

The Grizzly, February 9, 1990

Students Grapple With Rising Costs • USEAC Plants Seeds for First Ursinus Earth Day • Letter: Cynosure Cynic • Michener Bids Campus Adieu • The Trojans are Coming • Get your Act in Gear • Feb 14: A Woman\u27s Holiday? • UC Aquabears Squash Susquehanna • Susquehanna Drowned • Hoopsters Split Again • Making Tracks • Wismer Looking Gamely • Stop The Sex Wars • Grapplers Rebound With Big Victory • Gymnasts Prepare for Nationals • Athletes of the Week • Countdownhttps://digitalcommons.ursinus.edu/grizzlynews/1251/thumbnail.jp

Trisomy 21 induces pericentrosomal crowding delaying primary ciliogenesis and mouse cerebellar development.

Trisomy 21, the genetic cause of Down syndrome, disrupts primary cilia formation and function, in part through elevated Pericentrin, a centrosome protein encoded on chromosome 21. Yet how trisomy 21 and elevated Pericentrin disrupt cilia-related molecules and pathways, and the in vivo phenotypic relevance remain unclear. Utilizing ciliogenesis time course experiments combined with light microscopy and electron tomography, we reveal that chromosome 21 polyploidy elevates Pericentrin and microtubules away from the centrosome that corral MyosinVA and EHD1, delaying ciliary membrane delivery and mother centriole uncapping essential for ciliogenesis. If given enough time, trisomy 21 cells eventually ciliate, but these ciliated cells demonstrate persistent trafficking defects that reduce transition zone protein localization and decrease sonic hedgehog signaling in direct anticorrelation with Pericentrin levels. Consistent with cultured trisomy 21 cells, a mouse model of Down syndrome with elevated Pericentrin has fewer primary cilia in cerebellar granule neuron progenitors and thinner external granular layers at P4. Our work reveals that elevated Pericentrin from trisomy 21 disrupts multiple early steps of ciliogenesis and creates persistent trafficking defects in ciliated cells. This pericentrosomal crowding mechanism results in signaling deficiencies consistent with the neurological phenotypes found in individuals with Down syndrome