35of HSCs then re-enter circulation and seed their final destination in the kidney mar-
row (equivalent to the bone marrow in mammals).
Each stage of HSC development is regulated by extrinsic cues from the local and
systemic microenvironment. In this chapter, we will review the newest findings on
the niche factors critical for early hemogenic endothelial induction as well as HSC
specification, migration, and expansion. Understanding the key signals during
ontogeny is not only important to developmental biologists, but could also have
great clinical significance. Many of the players in embryonic niches are also impor-
tant in adult HSC biology, thus new discoveries from development could enlighten
the microenvironmental requirements necessary for maintaining adult HSC homeo-
stasis. Moreover, uncovering how HSCs are normally produced in the embryo will
help improve attempts to generate patient-specific HSCs from pluripotent stem cells
in vitro (reviewed in Kyba and Daley ( 2003 )).
4.2 Somite-Derived Niche Signals Promoting HSC Production
HSCs arise from specific mesoderm positioned in the posterior aspect of the embryo
and lateral to somitic mesoderm termed the posterior lateral mesoderm (PLM) (Ho
and Kimmel 1993 ). Recent work has demonstrated that this juxtaposition is critical
Hours 6 12 18 24 36 48 Days 3 5 adultAGM/DACHTKidneyHSC developmental timingICMAGM/DA CHTA.B.CVP/CHTCVDACVHSCCAFig. 4.1 The developmental timing and location of HSC development. (a) Timeline showing when
and where primitive and definitive hematopoietic induction occurs in zebrafish. (b) Schema showing
the location of the AGM/DA (left) and CHT (right) within zebrafish. Larger diagrams of the boxed
regions are shown on the bottom. ICM, inner cell mass, AGM aorta-gonad-mesonephros, DA dorsal
aorta, CHT caudal hematopoietic tissue, CA caudal artery, CV caudal vein, CVP caudal vein plexus
4 Developmental HSC Microenvironments: Lessons from Zebrafish