PUBLICATION

Drivers of Vessel Progenitor Fate Define Intermediate Mesoderm Dimensions by Inhibiting Kidney Progenitor Specification

Authors
Perens, E.A., Yelon, D.
ID
ZDB-PUB-240923-1
Date
2024
Source
Developmental Biology   517: 126-139 (Journal)
Registered Authors
Perens, Elliot, Yelon, Deborah
Keywords
hand2, npas4l, organ progenitor territories, osr1, vasculature, zebrafish
MeSH Terms
  • Gene Expression Regulation, Developmental/genetics
  • Stem Cells*/cytology
  • Stem Cells*/metabolism
  • Organogenesis/genetics
  • Mesoderm*/cytology
  • Mesoderm*/embryology
  • Mesoderm*/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Mice
  • Cell Differentiation/genetics
  • Basic Helix-Loop-Helix Transcription Factors*/genetics
  • Basic Helix-Loop-Helix Transcription Factors*/metabolism
  • PAX2 Transcription Factor/genetics
  • PAX2 Transcription Factor/metabolism
  • Animals
  • Transcription Factors*/genetics
  • Transcription Factors*/metabolism
  • Kidney*/cytology
  • Kidney*/embryology
  • Kidney*/metabolism
(all 23)
PubMed
39307382 Full text @ Dev. Biol.
Abstract
Proper organ formation depends on the precise delineation of organ territories containing defined numbers of progenitor cells. Kidney progenitors reside in bilateral stripes of posterior mesoderm that are referred to as the intermediate mesoderm (IM). Previously, we showed that the transcription factors Hand2 and Osr1 act to strike a balance between the specification of the kidney progenitors in the IM and the vessel progenitors in the laterally adjacent territory. Recently, the transcription factor Npas4l - an early and essential driver of vessel and blood progenitor formation - was shown to inhibit kidney development. Here we demonstrate how kidney progenitor specification is coordinated by hand2, osr1, and npas4l. We find that npas4l and the IM marker pax2a are transiently co-expressed in the posterior lateral mesoderm, and npas4l is necessary to inhibit IM formation. Consistent with the expression of npas4l flanking the medial and lateral sides of the IM, our findings suggest roles for npas4l in defining the IM boundaries at each of these borders. At the lateral IM border, hand2 promotes and osr1 inhibits the formation of npas4l-expressing lateral vessel progenitors, and hand2 requires npas4l to inhibit IM formation and to promote vessel formation. Meanwhile, npas4l appears to have an additional role in suppressing IM fate at the medial border: npas4l loss-of-function enhances hand2 mutant IM defects and results in excess IM generated outside of the lateral hand2-expressing territory. Together, our findings reveal that establishment of the medial and lateral boundaries of the IM requires inhibition of kidney progenitor specification by the neighboring drivers of vessel progenitor fate.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
el593
    		Small Deletion
    pd24TgTransgenic Insertion
      s5
        		Point Mutation
        s6
          		Deficiency
          sd28TgTransgenic Insertion
            sd63TgTransgenic Insertion
              1 - 6 of 6
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              No data available
              Fish
              No data available
              Antibodies
              Name Type Antigen Genes Isotypes Host Organism
              Ab2-pax2apolyclonal
                		IgGRabbit
                1 - 1 of 1
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                Orthology
                No data available
                Engineered Foreign Genes
                Marker Marker Type Name
                BFPEFGBFP
                EGFPEFGEGFP
                mCherryEFGmCherry
                1 - 3 of 3
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                Mapping
                No data available
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                Citation
                Perens, E.A., Yelon, D. (2024) Drivers of Vessel Progenitor Fate Define Intermediate Mesoderm Dimensions by Inhibiting Kidney Progenitor Specification. Developmental Biology. 517:126-139.