Lineage-specific control of convergent differentiation by a Forkhead repressor

Abstract

A central goal in developmental biology is to decipher the molecular events that govern cell fate specification in each developmental lineage. Here, we show that the C. elegans Forkhead transcription factor UNC-130 specifies two glial types that arise from one lineage, but does not affect equivalent glia that are produced in different anatomical regions from other lineages. We show that glial defects correlate with UNC-130:DNA binding, and that UNC-130 acts as a transcriptional repressor via two independent domains. UNC-130 can be functionally replaced by its human homolog, the neural crest lineage determinant FoxD3, and other neural crest factors (UNC-86/Brn3 and RNT-1/Runx) act in the same pathway. We propose that, in contrast to "terminal selectors", UNC-130 acts as a "lineage selector" to enable molecularly distinct progenitor cells to generate regionally equivalent cell types. This novel mechanism may underlie the recent observation of convergent lineages as a prevalent feature of vertebrate development.

Cell-type-specific promoters for C. elegans glia

“…Bacaj et al (2008);Braunreiter, Hamlin, & Lyman-Gingerich (2014);Heiman & Shaham (2009);Low et al (2019);Mizeracka, Rogers, Shaham, Bulyk, & Heiman (2019);Oikonomou et al (2011);Procko et al (2012Procko et al ( , 2011;Singhvi et al (2016);Wallace et al (2016);Yip & Heiman (2018) vap-1 (developmentally regulated) 2797 bp or 5205 bp promoterBacaj et al (2008); Ding et al (2015); Oikonomou et al (2011); Perens & Shaham (2005); Procko et al (2011); Wallace et al (2016); Wang et al (2017) Wang, D'Urso, & Bianchi (2012, 2008) T02B11.3 2.5 kb promoter Bacaj et al (2008); Grant, Matthewman, & Bianchi (2015); Mizeracka et al (2019); Oikonomou, Perens, Lu, & Shaham (2012) Oikonomou et al (2011); Procko et al (2011); Wang et al (2017, 2008) fig-1 2.2 kb promoter Bacaj et al (2008); Fenk & de Bono (2015); Kage-Nakadai et al (2016); Wallace et al (2016); Yoshida et al (2016) ver-1 (thermo-and dauer-regulated) 2110 bp promoter Popovici et al (2002); Procko et al (2012, 2011); Yoshida et al (2016) F53F4.13 650 bp promoter Bacaj et al (2008); Mizeracka et al (2019); Singhvi et al (2016) F11C7.2 350 bp promoter Bacaj et al (2008); Wallace et al (2016) hmit-1.2 (osmo-regulated) 979 bp promoter Kage-Nakadai et al (2016, 2011) lit-1 2.5 kb promoter Oikonomou et al (2011); Wallace et al promoter (from between exon 1 and exon 2) Gower et al (2001); Han et al (2013); Heiman & Shaham (2009); Mizeracka et al (2019); Sammut et al (2015); Tucker, Sieber, Morphew, & Han (2005); Wang et al (2017) grl-2 2981 bp promoter Hao et al (2006); Hunt-Newbury et al (2007); Low et al (2019); Mizeracka et al (2019); Molina-Garc ıa et al (2018); Sammut et al (2015) lin-48 6.8 kb promoter Johnson et al (2001); Mizeracka et al (2019); Molina-Garc ıa et al (2018) grd-15 840 bp promoter Hunt-Newbury et al (2007); Timbers et al (2016) unc-53 3.4 kb promoter (from exon 8 to exon 13) Stringham, Pujol, Vandekerckhove, & Bogaert (2002); Tucker et al (2005) et al (2016); Moussaif & Sze (2009); Ohkura & B€ urglin (2011); Perens & Shaham (2005); Wallace et al (2016) ztf-16 2.1 kb enhancer (from 4637 to 2536 bp upstream of ATG) Procko et al (2012); Sammut et al (2015) et al (2019); Col on-Ramos et al (2007); Gibson et al (2018); Ji et al (2019); Katz, Corson, Iwanir, Biron, & Shaham (2018); McMiller & Johnson (2005); Mizeracka et al (2019); Rapti et al (2017); Sammut et al (2015); Shao et al (2013); Stout & Parpura (2011); Yoshida et al (2016); Yoshimura et al (2008) swip-10 1.5 kb enhancer (from fifth intron, 1013 to 2504 bp downstream of ATG) Hardaway et al (2015) twk-16 3412 bp promoter Cianciulli et al (2019) ILso grl-18 2968 or 2962 bp promoter Cebul et al (2020); Hao et al (2006); Mizeracka et al (2019) Combinations of ILsh, ILso, OLsh, and OLso itx-1 2977 bp promoter or 1.8 kb promoter Haklai-Topper et al (2011); Han et al (2013); McQuary et al (2016); Sammut et al (2015) Gibson et al (2018); Hardaway et al (2015); Katz et al (2018); Oikonomou et al (2011); Rapti et al (2017); Sammut et al (2015); Wallace et al (2016); Yin et al (2017); Yoshida et al (2016); Yoshimura et al (2008) mir-228 2.2 kb promoter Molina-G...…”

Loss of the extracellular matrix protein DIG-1 causes glial fragmentation, dendrite breakage, and dendrite extension defects

“…Four neurons (AWA, AWB, AWC, AFD) form elaborate ciliated endings that are embedded in the wing-shaped portion of the sheath, while the others (ASE, ADF, ASG, ASH, ASI, ASJ, ASK, ADL) terminate in simple cilia that lie in a central lumenal channel [27,30]. Previous genetic screens have identified mutants that affect amphid sheath specification and cell body positioning [31], that disrupt extension of the amphid sheath glial process [9,22], or that lead to enlarged or supernumerary amphid sheath cells [32,33].…”

“…Previous genetic screens have identified mutants that affect amphid sheath specification and cell body positioning [31], that disrupt extension of the amphid sheath glial process [9,22], or that lead to enlarged or supernumerary amphid sheath cells [32,33].…”

Cell-type-specific promoters forC. elegansglia

“…S1B) and ADE and PDE socket glia in the body. Table 1 AMsh or PHsh F16F9.3 2 kb promoter (Bacaj et al, 2008;Braunreiter et al, 2014;Heiman and Shaham, 2009;Low et al, 2019;Mizeracka et al, 2019;Oikonomou et al, 2011;Procko et al, 2012Procko et al, , 2011Wallace et al, 2016;Yip and Heiman, 2018) vap-1 (developmentally regulated) 2797 bp or 5205 bp promoter (Bacaj et al, 2008;Ding et al, 2015;Oikonomou et al, 2011;Perens and Shaham, 2005;Procko et al, 2011;Wallace et al, 2016;Wang et al, 2017Wang et al, , 2012Wang et al, , 2008 2.5 kb promoter (Bacaj et al, 2008;Grant et al, 2015;Mizeracka et al, 2019;Oikonomou et al, 2012Oikonomou et al, , 2011Procko et al, 2011;Wang et al, 2017Wang et al, , 2008 fig-1 2.2 kb promoter (Bacaj et al, 2008;Fenk and de Bono, 2015;Kage-Nakadai et al, 2016;Wallace et al, 2016;Yoshida et al, 2016) ver-1 (thermo-and dauerregulated) 2110 bp promoter (Popovici et al, 2002;Procko et al, 2012Procko et al, , 2011Yoshida et al, 2016)...…”