Molecular and cellular basis of left–right asymmetry in vertebrates

Abstract

Although the human body appears superficially symmetrical with regard to the left–right (L-R) axis, most visceral organs are asymmetric in terms of their size, shape, or position. Such morphological asymmetries of visceral organs, which are essential for their proper function, are under the control of a genetic pathway that operates in the developing embryo. In many vertebrates including mammals, the breaking of L-R symmetry occurs at a structure known as the L-R organizer (LRO) located at the midline of the developing embryo. This symmetry breaking is followed by transfer of an active form of the signaling molecule Nodal from the LRO to the lateral plate mesoderm (LPM) on the left side, which results in asymmetric expression of Nodal (a left-side determinant) in the left LPM. Finally, L-R asymmetric morphogenesis of visceral organs is induced by Nodal-Pitx2 signaling. This review will describe our current understanding of the mechanisms that underlie the generation of L-R asymmetry in vertebrates, with a focus on mice.

Time-Course Transcriptional and Chromatin Accessibility Profiling Reveals Genes Associated With Asymmetrical Gonadal Development in Chicken Embryos

“…Previous studies revealed hundreds of side-biased genes in asymmetric gonadal development at the embryonic (E6, E9, and E12) and posthatching stages (D1); these genes include DAZL , GDF8 , PITX2 , PIWIL1 , and TDRD5 ( Intarapat and Stern, 2013 ; Wan et al, 2017 ; Zou et al, 2020 ), and these findings are consistent with our work. As the factor that determines left-right bias in vertebrates ( Amand et al, 1998 ; Piedra et al, 1998 ; Yoshioka et al, 1998 ; Schweickert et al, 2000 ; Dagle et al, 2003 ; Gormley and Nascone-Yoder, 2003 ; Grimes and Burdine, 2017 ; Hamada, 2020 ; Little and Norris, 2021 ), PITX2 has been proven to play a key role in gonadal lateralization and morphogenesis by regulating RALDH2 , SF1 and cyclin D1 expression, promoting cell proliferation and reorganizing the cytoskeleton. Besides, overexpression of PITX2 can rescue the degeneration of the right ovary during gonadogenesis ( Guioli and Lovell-Badge, 2007 ; Ishimaru et al, 2008 ; Rodríguez-León et al, 2008 ).…”

Cardiac Development: A Glimpse on Its Translational Contributions

“…Soon after the configuration of the cardiac straight tube, the first morphological left-right asymmetry arises as the heart is detached from the dorsal mesocardium and a rightward bending is invariably observed (Figure 2A). Molecular left-right asymmetry is initiated at earlier developmental stages emanating from the node [222] and transferred to the lateral plate mesoderm by distinct mechanisms including retinoic acid [223,224], Fgf [225][226][227], Bmp [228][229][230][231][232][233], Shh signaling [234] and non-coding RNAs [235,236] in a species-specific manner . This cascade ultimately converges on Nodal activation in the left lateral plate mesoderm (LPM) [248][249][250][251].…”

“…Impairment of sidedness leads to severe body plan abnormalities, including herein cardiac defects. Our knowledge of the molecular and cellular bases of left-right symmetry break has considerably increased over the last decade, providing novel links between early molecular events and impaired sidedness [222]. Such discoveries have served to unravel the genetic bases of heterotaxia and thus as guiding tools for genetic screening and counseling in these human conditions.…”

Essential Roles of Efferent Duct Multicilia in Male Fertility

“…Cilia are broadly classified into two types according to their microtubule composition: non-motile primary cilia with a 9 + 0 microtubule arrangement and motile multicilia with a 9 + 2 arrangement. The primary cilia in the embryonic node are a notable exception to this rule [4,5]. Nodal cilia, which are responsible for the establishment of the left-right body axis, have a 9 + 0 microtubule arrangement but show motility.…”