Dynamic expression of MMP28 during cranial morphogenesis

Abstract

Matrix metalloproteinases (MMPs) are a large family of proteases comprising 24 members in vertebrates. They are well known for their extracellular matrix remodelling activity. MMP28 is the latest member of the family to be discovered. It is a secreted MMP involved in wound healing, immune system maturation, cell survival and migration. MMP28 is also expressed during embryogenesis in human and mouse. Here, we describe the detailed expression profile of MMP28 in Xenopus laevis embryos. We show that MMP28 is expressed maternally and accumulates at neurula and tail bud stages specifically in the cranial placode territories adjacent to migrating neural crest cells. As a secreted MMP, MMP28 may be required in neural crest–placode interactions. This article is part of a discussion meeting issue ‘Contemporary morphogenesis’.

Paracrine regulation of neural crest EMT by placodal MMP28

“…MMP28 expression starts before the onset of neural crest migration ( Fig 1A and 1B ) and comparison with markers for neural crest ( sox8 and snai2 ), neural plate ( sox2 ), and placodes ( six1 ) ( Fig 1B and 1C ) confirms that MMP28 expression is restricted to the posterior part of the pan-placodal domain. In addition, a small neural crest domain, organised as a thin line along the edge of the neural fold, called the medial crest, also expressed MMP28 as we previously described [ 25 ]. MMP28 expression is then maintained in placodes at neural crest migration stages ( Fig 1D and 1E ).…”

“…We found that MMP28, a secreted metalloproteinase, is expressed in cranial placodes adjacent to the cephalic neural crest [ 25 ] and given the known importance of neural crest interaction with placodes for normal neural crest migration [ 26 ]; we decided to assess the putative role of placodal MMP28 for neural crest development. MMP28 expression starts before the onset of neural crest migration ( Fig 1A and 1B ) and comparison with markers for neural crest ( sox8 and snai2 ), neural plate ( sox2 ), and placodes ( six1 ) ( Fig 1B and 1C ) confirms that MMP28 expression is restricted to the posterior part of the pan-placodal domain.…”

“…The neural crest EMT program is often hijacked by invasive cells during carcinoma progression [ 23 , 24 ], making these cells an extremely relevant in vivo model to study EMT. Our data show that, during Xenopus development, MMP28 expressed in cranial placodes [ 25 ] is required for EMT of neural crest cells. MMP28 is secreted by placode cells, imported into the nucleus of adjacent neural crest cells where its catalytic activity is required for proper implementation of EMT via the maintenance of twist expression.…”

Identification of novel therapeutic target and prognostic biomarker in matrix metalloproteinase gene family in pancreatic cancer

“…It was initially cloned from keratinocyte, testis, and mixed tumor cDNA libraries 35 , 36 . Among normal tissues, MMP28 is relatively highly expressed in lung, testis, small intestine, and skin tissues 36 – 38 , and can participate in various pathophysiological processes such as inflammatory reaction, embryonic development, and angiogenesis 35 , 39 , 40 . Like other MMP s, aberrant upregulation of MMP28 has been reported in several carcinomas, including colorectal cancer 41 , gastric carcinoma 42 , 43 , and hepatocellular carcinoma 44 .…”

Contemporary morphogenesis

“…The extracellular matrix is a highly specialized mediator of multiple developmental processes, signalling to cells through modulating tissue stiffness or mediating bioavailability of secreted signalling molecules. Examples of how cell-matrix interactions promote morphogenesis include an overview of egg development in Drosophila [16] and insights into the spatiotemporal correlation of a matrix-remodelling MMP with migratory cell populations in the Xenopus laevis embryo [17].…”