Camille Velarde, Erica Landrau-Cribbs, Mahtab Soleimani, Theresa H Cruz
Measuring Policy, Systems, and Environmental Changes at Elementary Schools Involved in SNAP-Ed New Mexico Programming, 2018-2022
Preventing chronic disease
dna repair crucial genome stability developing cortex somatic de novo mutations cause neurological disorders however dna repair contributes neuronal development largely unknown address issue studied spatiotemporal roles dna polymerase pol key enzyme dna base excision repair pathway developing cortex using distinct forebrainspecific conditional knockout mice emx1crepolflfl nexcrepolflfl mice pol expression absent neural progenitors postmitotic neurons emx1crepolflfl mice whereas postmitotic neurons lacked pol expression nexcrepolflfl mice found dna doublestrand breaks dsbs frequently detected replication cortical progenitors emx1crepolflfl mice increased dsbs remained postmitotic cells resulted p53mediated neuronal apoptosis neuronal apoptosis caused thinning cortical plate although laminar structure normal addition accumulated dsbs also affected growth corticofugal axons commissural axons phenotypes observed nexcrepolflfl mice moreover cultured poldeficient neural progenitors exhibited higher sensitivity basedamaging agent methylmethanesulfonate resulting enhanced dsb formation similar damage found vitamin c treatment induces tet1mediated dna demethylation via 5hydroxymethylcytosine together genome stability mediated poldependent base excision repair crucial competence neural progenitors thereby contributing neuronal differentiation cortical development significance statement dna repair crucial development nervous system however dna polymerase poldependent dna base excision repair pathway contributes process still unknown found loss pol cortical progenitors rather postmitotic neurons led catastrophic dna doublestrand breaks dsbs replication p53mediated neuronal apoptosis resulted thinning cortical plate dsbs also affected corticofugal axon growth surviving neurons moreover induction base damage dna demethylation intermediates genome increased dsbs cultured poldeficient neural progenitors thus genome stability poldependent base excision repair neural progenitors required viability differentiation daughter neurons developing nervous system