The transcription factor GATA3 is a downstream effector of <i>Hoxb1</i> specification in rhombomere 4

Pata, Illar; Studer, Michèle; Doorninck, J. Hikke van; Briscoe, James; Kuuse, Sulev; Engel, JD; Grosveld, Frank; Karis, Alar

doi:10.1242/dev.126.23.5523

Cited by 98 publications

(11 citation statements)

References 50 publications

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“…The fact that hoxb1a expression persists at high levels until at least 24 hpf in zebrafish, and the lack of ectopic hoxb1a expression in the zbtb16a −/− ; zbtb16b −/− mutants, suggests that Zbtb16 is not regulating fgf3 through hoxb1. GATA2 and GATA3 specify r4 identity downstream of Hoxb1 in the mouse hindbrain ( Pata et al, 1999 ), and GATA4 mediates fgf3 upregulation upon retinoic acid (RA)-induced differentiation of F9 embryonal carcinoma cells into parietal endoderm ( Murakami et al, 1999 ), a cell type which also expresses hoxb1 ( Boylan et al, 1993 ). In a screen for downstream effectors of zebrafish hoxb1b , the protein phosphatase 1 regulatory subunit ppp1r14al , a potential regulator of GATA activity, was found to positively regulate fgf3 expression in r4 ( Choe et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Zbtb16 mediates a switch between Fgf signalling regimes in the developing hindbrain

Leino,

Constable,

Streit

et al. 2023

Development

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Developing tissues are sequentially patterned by extracellular signals that are turned on and off at specific times. In the zebrafish hindbrain, fibroblast growth factor (Fgf) signalling has different roles at different developmental stages: in the early hindbrain, transient Fgf3 and Fgf8 signalling from rhombomere 4 is required for correct segmentation, whereas later, neuronal Fgf20 expression confines neurogenesis to specific spatial domains within each rhombomere. How the switch between these two signalling regimes is coordinated is not known. We present evidence that the Zbtb16 transcription factor is required for this transition to happen in an orderly fashion. Zbtb16 expression is high in the early anterior hindbrain, then gradually upregulated posteriorly and confined to neural progenitors. In mutants lacking functional Zbtb16, fgf3 expression fails to be downregulated and persists until a late stage, resulting in excess and more widespread Fgf signalling during neurogenesis. Accordingly, the spatial pattern of neurogenesis is disrupted in Zbtb16 mutants. Our results reveal how the distinct stage-specific roles of Fgf signalling are coordinated in the zebrafish hindbrain.

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Section: Discussionmentioning

confidence: 99%

Zbtb16 mediates a switch between Fgf signalling regimes in the developing hindbrain

Leino,

Constable,

Streit

et al. 2023

Development

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“…The homeobox transcription factor hoxb1 is a known regulator of r4 identity (Studer et al, 1996; McClintock et al, 2002) and positively regulates fgf3 expression in r4 (Waskiewicz et al, 2002; Choe et al, 2011; Weicksel et al, 2014). GATA2 and GATA3 specify r4 identity downstream of Hoxb1 in the mouse hindbrain (Pata et al, 1999), and GATA4 mediates fgf3 upregulation upon retinoic acid-induced differentiation of F9 embryonal carcinoma cells into parietal endoderm (Murakami et al, 1999), a cell type which also expresses hoxb1 (Boylan et al, 1993). In a screen for downstream effectors of zebrafish hoxb1b , the protein phosphatase 1 regulatory subunit ppp1r14al , a potential regulator of GATA activity, was found to positively regulate fgf3 expression in r4 (Choe et al, 2011) Intriguingly, Plzf binds the mouse GATA4 regulatory region and upregulates its expression in heart cells (Wang et al, 2012b).…”

Section: Discussionmentioning

confidence: 99%

Plzf mediates a switch between Fgf signalling regimes in the developing hindbrain

Leino

Constable

Streit

et al. 2022

Preprint

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Developing tissues are sequentially patterned by extracellular signals that are turned on and off at specific times. In the zebrafish hindbrain, fibroblast growth factor (Fgf) signalling has different roles at different developmental stages: in the early hindbrain, transient Fgf3 and Fgf8 signalling from rhombomere 4 is required for correct segmentation, whereas later, neuronal Fgf20 expression confines neurogenesis to specific spatial domains within each rhombomere. How the switch between these two signalling regimes is coordinated is not known. We present evidence that the promyelocytic leukaemia zinc finger (Plzf) transcription factor is required for this transition to happen in an orderly fashion. Plzf expression is high in the early anterior hindbrain, then gradually upregulated posteriorly and confined to neural progenitors. In mutants lacking functional Plzf, fgf3 expression fails to be downregulated and persists until a late stage, resulting in excess and more widespread Fgf signalling during neurogenesis. Accordingly, the spatial pattern of neurogenesis is disrupted in plzf mutants. Our results reveal how the distinct stage-specific roles of Fgf signalling are coordinated in the zebrafish hindbrain.

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“…We show that GATA2, and its downstream effector GATA3 (refs. 18 , 19 ), are necessary to differentiate rhombomere 4 motor neurons (r4MNs) to IEEs but are dispensable for FBMN development. By contrast, a humanized cRE1 duplication mouse has ectopic expression of Gata2 in developing FBMNs and this phenotype is rescued by genetically ablating Gata3 .…”

Section: Mainmentioning

confidence: 99%

Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis

et al. 2023

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Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.

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The transcription factor GATA3 is a downstream effector of Hoxb1 specification in rhombomere 4

Cited by 98 publications

References 50 publications

Zbtb16 mediates a switch between Fgf signalling regimes in the developing hindbrain

Zbtb16 mediates a switch between Fgf signalling regimes in the developing hindbrain

Plzf mediates a switch between Fgf signalling regimes in the developing hindbrain

Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis

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