Biology subjects

Noël, E. S.

Publications and source records attributed to Noël, E. S..

3 recordsLinked to original sources

bioRxiv2024

morphoHeart: a novel quantitative tool to perform integrated 3D morphometric analyses of heart and ECM morphology during embryonic development

Heart development involves the complex structural remodelling of a linear heart tube into an asymmetrically looped and ballooned organ. Previous studies have associated regional expansion of extracellular matrix (ECM) space with tissue morphogenesis during development. We have developed morphoHeart, an 3D image tissue segmentation and morphometry software which delivers the first integrated 3D visualisation and multiparametric analysis of both heart and ECM morphology in live embryos. morphoHeart reveals that the ECM undergoes regional dynamic expansion and reduction during cardiac development, concomitant with chamber-specific morphological maturation. We use morphoHeart to demonstrate that regionalised ECM expansion driven by the ECM crosslinker Hapln1a promotes atrial lumen expansion during heart development. Finally, we have developed a GUI that allows the morphometric analysis tools of morphoHeart to be applied to z-stack images of any fluorescently-labelled tissue.

developmental biology↗

bioRxiv2023

Llgl1 mediates timely epicardial emergence and establishment of an apical laminin sheath around the trabeculating cardiac ventricle.

During heart development, the embryonic ventricle becomes enveloped by the epicardium, a layer of mesothelium which adheres to the outer apical surface of the heart. This is concomitant with onset of ventricular trabeculation, where a subset of cardiomyocytes lose apicobasal polarity and delaminate basally from the ventricular wall, projecting into the cardiac lumen to begin building the muscle mass necessary for adult cardiac function. Lethal(2) giant larvae homolog 1 (Llgl1) regulates the formation of apical cell junctions and apicobasal polarity, and we investigated its role in ventricular wall maturation, including trabeculation and epicardial establishment. We found that llgl1 mutant zebrafish embryos exhibit aberrantly positioned cardiomyocytes during early trabeculation, some of which extrude apically into the pericardial space. While investigating apical cardiomyocyte extrusion we identified a basal to apical shift in laminin deposition in the ventricular wall. Initially laminin deposition occurs on the luminal (basal) surface of the heart but concomitant with the onset of trabeculation basal laminin is removed and is instead deposited on the exterior (apical) surface of the ventricle. We find that epicardial cells express several laminin subunits as they adhere to the ventricular wall, and show that the epicardium is required for laminin deposition on the ventricular surface. In llgl1 mutants the timing of the basal-apical laminin shift is delayed, in line with a delay in establishment of the epicardial layer. Analysis of earlier epicardial development reveals that while both Llgl1 and laminin are not required for specification of the proepicardial organ, they are instead required for dissemination of epicardial cells to the ventricular surface. Together our analyses reveal an unexpected role for Llgl1 in correct timing of epicardial development, supporting integrity of the myocardial wall during early trabeculation.

developmental biology↗

bioRxiv2019

Asymmetric Hapln1a drives regionalised cardiac ECM expansion and promotes heart morphogenesis during zebrafish development

The mature vertebrate heart develops from a simple linear cardiac tube during early development through a series of highly asymmetric morphogenetic processes including cardiac looping and chamber ballooning. While the directionality of heart morphogenesis is partly controlled by embryonic laterality signals, previous studies have suggested that these extrinsic laterality cues interact with tissue-intrinsic signals in the heart to ensure robust asymmetric cardiac morphogenesis. Using live in vivo imaging of zebrafish embryos we describe a left-sided, chamber-specific expansion of the extracellular matrix (ECM) between the myocardium and endocardium at early stages of heart morphogenesis. We use Tomo-seq, a spatial transcriptomic approach, to identify transient and regionalised expression of hyaluronan and proteoglycan link protein 1a (hapln1a), encoding an ECM cross-linking protein, in the heart tube prior to cardiac looping overlapping with regionalised ECM expansion. Loss- and gain-of-function experiments demonstrate that regionalised Hapln1a promotes heart morphogenesis through regional modulation of ECM thickness in the heart tube. Finally, we show that while induction of asymmetric hapln1a expression is independent of embryonic left-right asymmetry, these laterality cues are required to orient the hapln1a-expressing cells asymmetrically along the left-right axis of the heart tube. Together, we propose a model whereby laterality cues position hapln1a expression on the left of the heart tube, and this asymmetric Hapln1a deposition drives ECM asymmetry and subsequently promotes robust asymmetric cardiac morphogenesis.

developmental biology↗