Abstract
The complexity of brain structure and function is rooted in the precise spatial and temporal regulation of selective developmental events. During neurogenesis, both vertebrates and invertebrates generate a wide variety of specialized cell types through the expansion and specification of a restricted set of neuronal progenitors. Temporal patterning of neural progenitors rests on fine regulation between cell-intrinsic and cell-extrinsic mechanisms. The rapid emergence of high-throughput single-cell technologies combined with elaborate computational analysis has started to provide us with unprecedented biological insights related to temporal patterning in the developing central nervous system (CNS). Here, we present an overview of recent advances in Drosophila and vertebrates, focusing both on cell-intrinsic mechanisms and environmental influences. We then describe the various multi-omics approaches that have strongly contributed to our current understanding and discuss perspectives on the various -omics approaches that hold great potential for the future of temporal patterning research.
Highlights
During central nervous system (CNS) development, undifferentiated cells initially divide to generate highly diverse cell types, within and across species
Temporal regulation over the biological processes that underlie the accurate assembly of a functional CNS is becoming increasingly understood
Further investigations on the epigenetic mechanisms through which temporal progression is regulated will deepen our understanding of cell-intrinsic aspects
Summary
During CNS development, undifferentiated cells initially divide to generate highly diverse cell types, within and across species. The production and proper assembly of CNS cells into functional networks rely on the interplay between intrinsic temporally regulated programs and extracellular timing signals. Neural progenitor cells undergo temporal fate specification and sequentially produce distinct types of neurons, which progressively populate the developing CNS. One of these temporal transitions occurs upon the proliferative (symmetric) to neurogenic (asymmetric) switch in the division mode of first neuroepithelial cells (NEs) and apical radial glial cells (aRGs) [5]. We will discuss key principles defining the temporal progression of cell identity and the extracellular timing signals driving CNS development. ENueruarladl edveevleolpopmmeennttininDDrorossoopphhiillaa aanndd iinn tthhee mmaammmmaalliiaann cceerreebbrraallccoorrtetexx. BThpuosp, uthlaetiNonB is selfp-orepnuelwateiodnuips osnelfe-arechnedwiveidsiuopno, nadedaicthiodniavlilsyioynie, laddindgitiaondaislltyinycitecldelilntgypaed:i(sit)inTcytpcee-l0l tdyipveis:i(oi)nsTydpiree-c0tly givdeivbiisritohntso dairdeicfftelyregnitviaetibnigrtnhetuoroan,d(iifif)eTreynpteia-t1indgivniseiuornosnp, r(oiid) uTcyepgea-1ngdliiovnisimonosthperrocdeullcsethgaant gfulirotnher divmidoethoenrceceilnlstothtwatofnueruthreornsdievaicdhe, aonndce(iiini)toTytpweo-2ndeiuvriosniosnesagcehn, earnadte(iiniit)erTmypede-i2atdeinveisuioranlspgroengeernaitteors (INiaPnp)t,errwomlhoeindcghiea,dtiensneteuruirernsa,lofpfurraotshgyeemrnmigtoievrtesri(rcIiNsdeiPvt)io,swigoahnniscgh[l7,i–oin9n]t.muNronet,uhfreuorrgtcheenellerssgioisvvoeecrrciauserpstrooinlgoatnwnggoeldisoensqeumreieonstthioaeflrawcseaylvlmseosm:ve(eitr)ric divdisuiroinnsg[t7h–e9e].mNberyuorongicenpehsaisseoacncdur(siii)nthtwroougsehqouuetnthtieallawrvaavleas:nd(i)pduuprailnsgtathgeese, minbpryreopnaircaptihoansfeoarntdhe(ii) thrfoiungalhmouettatmheolraprhvoasliasn[1d0p,1u1p].aElmstbargyeosn, iinc nperueproagraentieosnisfoisrathoenefi-ndaalymloentagmeovrepnht odsuirsin[1g0w,11h]i.chEmdibstriynocnt ic neuNrBogteynpeessistriasnasiotinoen-dtharyoulognhgaecvaesncatddeuorifntgemwphoircahl dtriasntisnccritpNtiBontyfapcetsortsra(ntTsFitsi)ongivthinrogurgishe atocaassceardieesof temopf orreasltrtircatnedsclriinpetaiognesf.acTthoerss(htoTrFtsl)egnigvtihngofritsheistonaeuserroigeesnoifcrwesatrviectuedndlienreliaegsetsh.eTphreeschisoertNleBn-igntthrionfsitchis neuteromgpeonriaclwparovgeruenssdioernl.ieAstththeepernecdisoefNemB-binrytroignesnicetseism, pthoeraml apjroorgitryesosfioNnB. sAutnthdeeregnodaopfoepmtobsriys,owgehnileesis, thefemwaejonrtietryGo1fqNuBiesscuenncdee[r1g2o].aBpyotphteobseisg,inwnhinilgeoffetwheelnatrevralGst1agqeu,iseusrcveinvcineg[1N2B].s eBxyittqhueiebsecgenincne ianngdof theinlaitrivatael astsaegceo,nsdu, rlovnivgienrgwNavBesoefxniteuqruoigeesncensicse, sapnadnnininitgiabtoetha tsheecolanrdva, loangdepruwpalvsetaogfense[1u0r,o1g1e,1n3e].sis, spanning both the larval and pupal stages [10,11,13]
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