472 The maternal-to-zygotic transition in embryonic patterning of Caenorhabditis elegans Erin D Newman-Smith* and Joel H Rothmanf Maternal factors laid down in the oocyte regulate blastomere identities in the early Caenorhabdihs elegans embryo by activating zygotic patterning genes and restricting their expression to the appropriate lineages. A number of early- acting zygotic genes that specify various cell fates have been identified recently and their temporal and spatial regulation by maternal factors has begun to be elucidated. Addresses Department of Molecular, Cellular and Developmental Biology and Neuroscience Research Institute, University of California - Santa Barbara, Santa Barbara, California 93106, USA *e-mail: newman@lifescl.lscf.ucsb.edu +e-mall: rothman@lifesci.lscf.ucsb.edu Current Opinion in Genetics & Development 1998, 8:472-480 http://biomednet.com/elecref/0959437X00800472 :c~ Current Biology Publlcafions ISSN 0959-437X Abbreviations EDR endoderm-determinlng region RNAi RNA-mediated interference RNAP RNA polymerase Introduction zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA (kne tic approaches ha\,c made it possible to identify many of the molecular regulators that specify early embr);- onic c e ll fa te s in the nematode ~kwo~hrtll dqpxs. ‘I’hc asymmetr)- of early c e ll di\*isions, orientation of spindles, and partitioning of macromolecules during the early deal-- ages are dire c te d by ina tc rna lly provided components. many of \vhich ha\,e been molecularly identified in the psc several years (see [ 1.21 for rcviavs). ‘I‘hesc factors direct the as)mmctric ccl1 divisions that form the six founder cells - X13, I<. JIS, (:, 11 and I’, - each of lvhich gives rise to a distinct set of differentiared cell types (Figure 1) [.3]. ‘I’he resultanr as)mmetrics in the cmbry Icad to rhe differential expression and/or activity of mater- na lly encoded regulators that control the identities of earl) \)laswtieres (see [4’] for 3 recent re\-iav). ILlost of these larter m:lternal factors are apparent transcription facrors, implying that they function to regulate the expression of zygotic (i.e. embryonically transcribed) genes. \t,hich then assume control of cmtqonic pattcrning. 6’. e/quv/s is one of only :I few orpnisms for which this transition from marcr- nal to zyg:oGc control of cell fate specification has been un\,eiled. Kcccnt rc\.iews have described maternal control of early cell fate specification [4’,5] and transcriptional rcg- ulator); mechanisms in C. u/qyu~~ [6]. Here, MT &scribe some of the recently identified z?;gotic genes that regulate pathways of differentiation during early embryogenesis and, Mhere knouq their regulation by mawrnal factors (e.g. see ‘I:,lblC 1). The zygotic genome is not required for the timing and pattern of early embryonic cleavages \Vhereas zygotic transcription of at lust some genes begins by the four-ccl1 stage in C’. &um.s [7], p ha rm a c o lo g - ic a l and genetic experiments suggest that zygotic gcncs are not required until later in embtygenesis [X-10]. hlaternal components are apparentI\ sufficient to direct the embryo through the initial cleavage rounds and up to approximately the onser of gastrulation at the 2X-cell stage. Inhibition of RNA polymerase II (KN,W 11) activit?. either with a-amanitin [O]. or by KNh-mediated intcrfcr- ence (RNAi; [l zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM 1'1) of the crmtc-l gcnc (the suuct~~r:II gcnc for the largest RNAI’ II subunit) [lo]. resulred in no con- spicuous defects in the timing or pattern of the inirial cleavages up to the ZfXell stage. Embryonic dcvelopmenr is subsequently affected and embryos arrested at the -100 cell stage, far short of the 5.58 cells prcscnt in a normal uni- mal at the end of cmbryogencsis. ‘I‘he first defects seen in embryos lacking KN,W II acti\+ ty is the mis-specification of the I< (endoderm) lineage: the daughters of the K founder cell do not exhibit proper spin- dlc rotation or cell-cycle lengthening and fail to cntcr the in&or of the embryo [lo] (i.e. gastrulation is not iniriat- ed). ‘I’hus, although it is possible that some /.ygoricall~~ dircctcd processes are a-amanitin- or NNU-I Kk,\i-inscnsi- ri\z, or their absence does not C;IWX an early obscr\.ablc defect, it appears that uanscription of zygotic gcncs i\ not generally required for creating the asymmetries in the prc- gastrulation embryo. Specification of the E-ccl1 idcntit?; and presumably suhscquent c\.ents, dots ruluirc the activity of zygotic gcncs. (knctic analyses have further supported the conclusion that etirly dc\.elopmcnt is not dependenr on zygotiwll~ expressed genes. Scvcral laboratories ha\ e raltcn ad\ an- tage of deficiencies (chromosomal deletions) to scan mo\t of the genome for genetic regions rrclLlired for normal embryonic devclopmenr [12-161. I<nibryos homoz\:go~is for each of a numhcr of dcficiencics that collccti\.cly rcp- resent most of the gcnome progress through early (p-gas- trula tio n) c \ znts no rm a lly; most siic h d e fic ie nc y c m b r)o s a rre st during la te r d c \ rlo p m c nt. ‘I’hese d e fic ie nc y sc rc c n5 ha w id e ntifie d g e no m ic re g io ns ne c e ssa ry fo r m o rp ho g c n- e sis, c e ll- c yc le c o nuo l, e p id c rm a l and m usc le dcvclol3- mcnt, cpithelial patterning, and specification of the endoderm - demonstrating the widcsprcad in\wlvcmcnt of zygotic genes in these processes [ 12-16.17”]. How is the transition from maternal to Lygotic control of development orchestrated? Although this process is nor