Localization of Apaf1 gene expression in the early development of the mouse by means of in situ reverse transcriptase‐polymerase chain reaction

Abstract

Apoptosis is an essential ubiquitous process that controls the duration of the life span of cells, thus playing a crucial role in morphogenetic, histogenetic, and phylogenetic developmental processes. Apaf1 (apoptosis protease activating factor 1) is one of the central mediators of the intrinsic apoptotic pathway and a part of the apoptosome, which activates procaspase-3 and promotes cell death. Gene knockout of Apaf1 in mice leads to late embryonic lethality with malformations such as the persistence of interdigital webs and hyperplasia of brain and retina. Therefore, Apaf1 is generally believed to play a crucial role in developmental apoptosis and have a widespread expression. However, its pattern of expression in early development remains unknown. To specify whether Apaf1 indeed plays this key role, we investigated the pattern of gene expression for Apaf1 in mouse embryos on day 7, 9, and 12 of development. Our results show, that gene expression for Apaf1 first occurs within the embryo between day 7 and 9 of development, becoming more widespread toward day 12 and then includes structures, such as yolk sac, mesenchyme, cartilage, heart anlage, otic vesicle, peridermis, and anlagen of the spinal ganglia and vertebral bodies. Our results also show that gene expression for Apaf1 is not ubiquitous in early mouse development. This finding indicates that cell death processes are independent of or less dependent on Apaf1 during this time. Of interest, an active gene expression for Apaf1 is also present in organ anlagen such as heart or intestine, in which no obvious phenotype is seen after Apaf1 deletion. This finding suggests a possible role for Apaf1 in such anlagen as a putative alternative compensatory pathway, which could be switched on in the case of defects in the mediators that are normally involved in such organs. Developmental Dynamics 234:215-221, 2005.

RNA Profiles of Porcine Embryos during Genome Activation Reveal Complex Metabolic Switch Sensitive to In Vitro Conditions

“…APAF1 (apoptotic peptidase activating factor 1) is a crucial component of apoptosome [89] and was found to be responsible for programmed cell death starting between embryonic day 7 and 9 in mouse [90], [91]. This finding cannot explain its abundant presence at 2-cell stage.…”

Identification of a nonsense mutation in APAF1 that is likely causal for a decrease in reproductive efficiency in Holstein dairy cattle

“…Results of the functional annotation analysis using ANNOVAR (Wang et al, 2010) BTA5 region [62,435,597,776] Genes listed for SNP located within intergenic regions are the closest genes that flank the corresponding intergenic SNP. interdigital webs, and craniofacial malformations (Cecconi et al, 1998;Yoshida et al, 1998;Honarpour et al, 2001;Müller et al, 2005). Significantly, the deletion of 670 C-terminal amino acids from the APAF1 polypeptide removes 15 WD40 repeats that form a predicted functional WD40 domain in the cattle protein.…”

Allele Frequency of APAF1 Mutation in Holstein Cattle in Brazil

“…The APAF 1 (apoptotic protease activating factor-1) protein is an important molecule in the cell apoptosis process ( 1 ) and central nervous system development during embryogenesis ( 2 ). The mutation is an autosomal recessive inherited disease, associated with HH1 and characterized by a substitution of cytosine for a thymine (c.1741C>T) in chromosome 5 ( 3 ).…”