title: Hand2 regulates extracellular matrix remodeling essential for gut-looping morphogenesis in zebrafish.
abstract: Extracellular matrix (ECM) remodeling is critical for organogenesis, yet its molecular regulation is poorly understood. In zebrafish, asymmetric migration of the epithelial lateral plate mesoderm (LPM) displaces the gut leftward, allowing correct placement of the liver and pancreas. To observe LPM migration at cellular resolution, we transgenically expressed EGFP under the control of the regulatory sequences of the bHLH transcription factor gene hand2. We found that laminin is distributed along the LPM/gut boundary during gut looping, and that it appears to become diminished by the migrating hand2-expressing cells. Laminin diminishment is necessary for LPM migration and is dependent on matrix metalloproteinase (MMP) activity. Loss of Hand2 function causes reduced MMP activity and prolonged laminin deposition at the LPM/gut boundary, leading to failed asymmetric LPM migration and gut looping. Our study reveals an unexpected role for Hand2, a key regulator of cell specification and differentiation, in modulating ECM remodeling during organogenesis.
authors.affiliation: Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics, and Human Genetics, Cardiovascular Research Institute, Liver Center, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Chunyue
authors.initials: C
authors.lastname: Yin
authors.forename: Kazu
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Tatiana
authors.initials: T
authors.lastname: Hochgreb
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Poss
authors.forename: Didier Y R
authors.initials: DY
authors.lastname: Stainier
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D019521:Body Patterning / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D038081:Organogenesis / Q000502:physiology*; D019076:Transgenes / Q000235:genetics; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D007797:Laminin; D020782:Matrix Metalloproteinases; D029961:Zebrafish Proteins; C485184:enhanced green fluorescent protein; C410915:hand2 protein, zebrafish