Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

Abstract

Neves, Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ f o r m a t i o n , Developmental Biology, http://dx.doi.org/10. 1016/j.ydbio.2016.08.012 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe avian thymus and parathyroids (T/PT) common primordium derives from the endoderm of the third and fourth pharyngeal pouches (3/4PP). The molecular mechanisms that govern T/PT development are not fully understood. Here we study the effects of Notch and Hedgehog (Hh) signalling modulation during common primordium development using in vitro, in vivo and in ovo approaches. The impairment of Notch activity reduced Foxn1/thymus-fated and Gcm2/Pth/parathyroid-fated domains in the 3/4PP and further compromised the development of the parathyroid glands. When Hh signalling was abolished, we observed a reduction in the Gata3/Gcm2-and Lfng-expression domains at the median/anterior and median/posterior territories of the pouches, respectively. In contrast, the Foxn1 expression- This study offers novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner.

Thymus Inception: Molecular Network in the Early Stages of Thymus Organogenesis

“…Several of the Notch signaling receptors, ligands, modulators, and target genes are expressed in the pharyngeal arch region at stages of T/PT common primordium development [70,75,131,145]. In chicken embryos, Notch1 and the ligand Delta1 are faintly expressed in endoderm and neighboring cells of the 3PP.…”

“…The Notch targets, Hes1 and Hey1, are downstream of Tbx1 and Foxi3 in the development of the pharyngeal structures [70,145], and Hes1 is required for organs migration to their final destination [131]. Other Notch target genes, Hes5.1, Hes6.1, and Gata3, are expressed in the pharyngeal region of avian embryos [75]. In particular, Gata3 is expressed in T/PT common primordium and afterward is restricted to the Gcm2-domain when Foxn1-domain is established, both in chicken and mouse [73][74][75].…”

“…Other Notch target genes, Hes5.1, Hes6.1, and Gata3, are expressed in the pharyngeal region of avian embryos [75]. In particular, Gata3 is expressed in T/PT common primordium and afterward is restricted to the Gcm2-domain when Foxn1-domain is established, both in chicken and mouse [73][74][75]. Gata3 −/− mice embryos lack Gcm2 expression and do not develop the T/PT primordia, while Gata3 +/− heterozygotes display smaller T/PT primordia with fewer Gcm2-expressing cells [73].…”

“…Hh ligands act as morphogens, signaling both at short range and over many cell diameters [147]. The synthesis of Hh ligand and receptor, sonic hedgehog (Shh), and of the protein patched homolog 1 (Ptch1), are mainly restricted to the anterior pouches region, both in chicken and mouse embryos [75,87,88]. By the time Gcm2 starts being expressed, Shh is present throughout the pharyngeal endoderm, with the exception of the pharyngeal pouches [75,87,88].…”

Nodal and Hedgehog synergize in gill slit formation during development of the cephalochordate Branchiostoma floridae

“…The second, third and fourth pharyngeal arches are small (Moore-Scott and Manley, 2005). Like Nodal, Shh signaling is also required for normal development of the thyroid (Fagman et al, 2004;Moore-Scott and Manley, 2005;Bain et al, 2016;Figueiredo et al, 2016). Nodal and Hh cooperate in patterning the mesoderm, but whether they act together or in parallel in thyroid development has not been addressed.…”